This represents a collaborative program for the study of the immunology of leprosy and leishmania. Dr. Convit's wide experience in both diseases and unique clinical research program in developing immunotherapeutic and immunoprophylactic trials in leprosy patients and in patients with diffuse cutaneous leishmaniasis provide a unique clinical and experimental resource for these immunologic studies. The aims of this proposal are to develop an understanding of the mechanism of the selective unresponsiveness underlying lepromatous leprosy and diffuse cutaneous leishmaniasis, and in particular in characterizing suppressor cells and antigen presentation in these patients. Changes in these immunologic functions upon immunotherapy will be studied. A second aim will be to define the cytocidal mechanisms of macrophages required for killing the respective causative organisms, particularly oxidative cytocidal mechanisms, and examining the lesions across the spectrum of these diseases to analyze for defects in killing. In addition, the role of macrophages in producing tissue damage in leprosy and mucocutaneous leishmaniasis will be explored. Finally, sero- and cellular epidemiologic studies will be carried out using monoclonal antibodies to specific antigens of the pathogen and suppressor assays to identify individuals at high risk in a contact population for developing lepromatous leprosy, and for assessing the immunological changes brought about by vaccine.